Orientation in upper gastrointestinal endoscopy—the only way is up

BACKGROUND Oesophagogastroduodenoscopy is the gold standard investigation for the upper gastrointestinal (UGI) tract. Orientation during endoscopy is challenging and United Kingdom training focusses on technical competence and procedural safety. The reported location of UGI pathologies is crucial to post-endoscopic planning. AIM To evaluate endoscopists’ ability to spatially orientate themselves within the UGI tract. METHODS A cross sectional descriptive study elicited, using an anonymised survey, the ability of endoscopists to orientate themselves within the UGI tract. The primary outcome was percentage of correct answers from all surveyed; secondary outcomes were percentage of correct answers from experienced vs novice endoscopists. Pearson’s χ2 test was applied to compare groups. RESULTS Of 188 respondents, 86 were experienced endoscopists having completed over 1000 endoscopies. 44.4% of respondents correctly identified the anterior stomach and 47.3% correctly identified the posterior of the second part of the duodenum (D2). Experienced endoscopists were significantly more likely than novice to identify the anterior stomach correctly [61.6% vs 31.3%, X2 (1, n = 188) = 11.10, P = 0.001]. There was no significant difference between the two groups in identifying the posterior of D2. CONCLUSION The majority of endoscopists surveyed were unable to identify key landmarks within the UGI tract. Endoscopic orientation appears to improve with experience yet there are some areas still not well recognised. This has potential considerable impact on post-endoscopic management of patients with posterior duodenal ulcers being more likely to perforate and associated with a higher rebleeding risk. We suggest the development of a consensus statement on endoscopic description

How much noise can be added in cardiac X-ray imaging without loss in perceived image quality?

Dynamic X-ray imaging systems are used for interventional cardiac procedures to treat coronary heart disease. X-ray settings are controlled automatically by specially-designed X-ray dose control mechanisms whose role is to ensure an adequate level of image quality is maintained with an acceptable radiation dose to the patient. Current commonplace dose control designs quantify image quality by performing a simple technical measurement directly from the image. However, the utility of cardiac X-ray images is in their interpretation by a cardiologist during an interventional procedure, rather than in a technical measurement. With the long term goal of devising a clinically-relevant image quality metric for an intelligent dose control system, we aim to investigate the relationship of image noise with clinical professionals’ perception of dynamic image sequences. Computer-generated noise was added, in incremental amounts, to angiograms of five different patients selected to represent the range of adult cardiac patient sizes. A two alternative forced choice staircase experiment was used to determine the amount of noise which can be added to a patient image sequences without changing image quality as perceived by clinical professionals. Twenty-five viewing sessions (five for each patient) were completed by thirteen observers. Results demonstrated scope to increase the noise of cardiac X-ray images by up to 21% ± 8% before it is noticeable by clinical professionals. This indicates a potential for 21% radiation dose reduction since X-ray image noise and radiation dose are directly related; this would be beneficial to both patients and personnel

Does computer-aided diagnostic endoscopy improve the detection of commonly missed polyps? A meta-analysis

Background/Aims Colonoscopy is the gold standard diagnostic method for colorectal neoplasia, allowing detection and resection of adenomatous polyps; however, significant proportions of adenomas are missed. Computer-aided detection (CADe) systems in endoscopy are currently available to help identify lesions. Diminutive (≤5 mm) and nonpedunculated polyps are most commonly missed. This meta-analysis aimed to assess whether CADe systems can improve the real-time detection of these commonly missed lesions. Methods A comprehensive literature search was performed. Randomized controlled trials evaluating CADe systems categorized by morphology and lesion size were included. The mean number of polyps and adenomas per patient was derived. Independent proportions and their differences were calculated using DerSimonian and Laird random-effects modeling. Results Seven studies, including 2,595 CADe-assisted colonoscopies and 2,622 conventional colonoscopies, were analyzed. CADe-assisted colonoscopy demonstrated an 80% increase in the mean number of diminutive adenomas detected per patient compared with conventional colonoscopy (0.31 vs. 0.17; effect size, 0.13; 95% confidence interval [CI], 0.09–0.18); it also demonstrated a 91.7% increase in the mean number of nonpedunculated adenomas detected per patient (0.32 vs. 0.19; effect size, 0.05; 95% CI, 0.02–0.07). Conclusions CADe-assisted endoscopy significantly improved the detection of most commonly missed adenomas. Although this method is a potentially exciting technology, limitations still apply to current data, prompting the need for further real-time studies

Modelling forced vital capacity in idiopathic pulmonary fibrosis: optimising trial design.

INTRODUCTION: Forced vital capacity is the only registrational endpoint in idiopathic pulmonary fibrosis clinical trials. As most new treatments will be administered on top of standard of care, estimating treatment response will become more challenging. We developed a simulation model to quantify variability associated with forced vital capacity decline. METHODS: The model is based on publicly available clinical trial summary and home spirometry data. A single, illustrative trial setting is reported. Model assumptions are 400 subjects randomised 1:1 to investigational drug or placebo over 52 weeks, 50% of each group receiving standard of care (all-comer population), and a 90-mL treatment difference in annual forced vital capacity decline. Longitudinal profiles were simulated and the impact of varying clinical scenarios evaluated. RESULTS: Power to detect a significant treatment difference was 87-97%, depending on the analysis method. Repeated measures analysis generally outperformed analysis of covariance and mixed linear models, particularly with missing data (as simulated data were non-linear). A 15% yearly random dropout rate led to 0.6-5% power loss. Forced vital capacity decline-related dropout introduced greater power loss (up to 12%), as did subjects starting/stopping standard of care or investigational drug. Power was substantially lower for a 26-week trial due to the smaller assumed treatment effect at week 26 (sample size would need doubling to reach a power similar to that of a 52-week trial). CONCLUSIONS: Our model quantifies forced vital capacity decline and associated variability, with all the caveats of background therapy, permitting robust power calculations to inform future idiopathic pulmonary fibrosis clinical trial design. FUNDING: Galapagos NV (Mechelen, Belgium)

A new MBE CdTe photoconductor array detector for X-ray applications

A CdTe photoconductor array x-ray detector was grown using Molecular Beam Epitaxially (MBE) on a Si (100) substrate. The temporal response of the photoconductor arrays is as fast as 21 psec risetime and 38 psec Full Width Half Maximum (FWHM). Spatial and energy responses were obtained using x-rays from a rotating anode and synchrotron radiation source. The spatial resolution of the photoconductor was good enough to provide 75 {micro}m FWHM using a 50 {micro}m synchrotron x-ray beam. A substantial number of x-ray photons are absorbed effectively within the MBE CdTe layer as observed from the linear response up to 15 keV. These results demonstrate that MBE grown CdTe is a suitable choice of the detector materials to meet the requirements for x-ray detectors in particular for the new high brightness synchrotron sources

How much image noise can be added in cardiac x-ray imaging without loss in perceived image quality?

YesCardiologists use x-ray image sequences of the moving heart acquired in real-time to diagnose and treat cardiac patients. The amount of radiation used is proportional to image quality; however, exposure to radiation is damaging to patients and personnel. The amount by which radiation dose can be reduced without compromising patient care was determined. For five patient image sequences, increments of computer-generated quantum noise (white + colored) were added to the images, frame by frame using pixel-to-pixel addition, to simulate corresponding increments of dose reduction. The noise adding software was calibrated for settings used in cardiac procedures, and validated using standard objective and subjective image quality measurements. The degraded images were viewed next to corresponding original (not degraded) images in a two-alternativeforced- choice staircase psychophysics experiment. Seven cardiologists and five radiographers selected their preferred image based on visualization of the coronary arteries. The point of subjective equality, i.e., level of degradation where the observer could not perceive a difference between the original and degraded images, was calculated; for all patients the median was 33% 15% dose reduction. This demonstrates that a 33% 15% increase in image noise is feasible without being perceived, indicating potential for 33% 15% dose reduction without compromising patient care.Funded in part by Philips Healthcare, the Netherlands. Part of this work has been performed in the project PANORAMA, co-funded by grants from Belgium, Italy, France, the Netherlands, and the United Kingdom, and the ENIAC Joint Undertaking

A novel allosteric modulator of the cannabinoid CB1 receptor ameliorates hyperdopaminergia endophenotypes in rodent models

Funding and disclosure The authors declare the following financial and biomedical conflict of interests: Ruth A. Ross, Catharine A. Mielnik, Amy J. Ramsey, Iain R. Greig, Laurent A. Trembleau, Mostafa H. Abdelrahman are co-inventors on a patent application related to ABM300 and structural analogs. Kim S. Sugamori, David B. Finlay, Hayley H.A. Thorpe, Matthieu Schapira, Nirunthan Sivananthan, Chun Kit Li, Vincent M. Lam, Sean Harrington, W. McIntyre Burnham, Jibran Y. Khokhar, Ali Salahpour, Michelle Glass reported no biomedical financial interests or potential conflicts of interest. W. McIntyre Burnham received Δ9- (THC) as a gift from MedReleaf. The authors would like to gratefully acknowledge Wendy Horsfall for mouse colony maintenance. The work was funded by grants to RAR from CIHR (PPP-125784, PP2-139101), CIHR funding to AJR (MOP119298) and CIHR funding to AS (PJT-15619).Peer reviewedPostprintPublisher PD

Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract

Objectives: The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load. Methods: COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString nCounter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time. Results Eighty-two subjects (50% female, median age 54 years (range 3–73)) with COVID-19 were recruited. Paired URT viral load samples were available for 16 blood transcriptome samples, and 17 respiratory epithelial transcriptome samples. Natural Killer (NK) cells were the only blood cell type significantly correlated with URT viral load z-scores (r = −0.62, P = 0.010). Twenty-four blood gene expression modules were significantly correlated with URT viral load z-score, the most significant being a module of genes connected around IFNA14 (Interferon Alpha-14) expression (r = −0.60, P = 1e-10). In fixed repertoire analysis, prostanoid-related gene expression was significantly associated with higher viral load. In nasal epithelium, only GNLY (granulysin) gene expression showed significant negative correlation with viral load. Conclusions: Correlations between the transcriptional host response and inter-individual variations in SARS-CoV-2 URT viral load, revealed many molecular mechanisms plausibly favouring or constraining viral replication. Existing evidence corroborates many of these mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production and administration of interferon alpha-14 may be attractive transmission-blocking interventions

The Role of Physical Activity Prescription in Cardiovascular Disease Prevention Amongst South Asian Canadians

Unequivocal evidence suggests an increased prevalence of cardiovascular disease (CVD) amongst South Asian Canadians (SACs) compared to other ethnic cohorts, due to a combination of their unique cardiometabolic profile and environmental factors. This unfavorable CVD profile is characterized by an elevated risk of dyslipidemia, high apolipoprotein B/apolipoprotein A1 ratio, hypertension, glucose intolerance, type 2 diabetes mellitus, as well as increased BMI, body fat percentage, abdominal and visceral adiposity. Despite the overwhelming evidence for the effectiveness of physical activity (PA) in circumventing the onset of CVD and in the reduction of CVD risk factors, SACs are among the most physically inactive cohorts in Canada. This relates to a set of common and unique socio-cultural barriers, such as gender, beliefs and perceptions about illness, immigration, unfavorable PA environments, and their high prevalence of debilitating chronic diseases. Several strategies to improve PA participation rates in this high-risk population have been suggested, and include the implementation of culturally sensitive PA interventions, as well as clinician training in PA prescription through workshops that emphasize knowledge translation into clinical practice. Therefore, the purpose of this mini-review is to highlight and discuss: (1) the burden of heart disease in SACs (2) the cardiovascular benefits of PA for SACs; (3) factors affecting PA participation among SACs and how they can be addressed; (4) the impact of culturally sensitive PA prescription on CVD prevention; (5) barriers to culture-specific PA prescription by clinicians, and strategies to improve its use and impact